Searching for Novel Endophenotypic Markers for Bipolar Disorder

Intra-subject variability in reaction time (ISVRT) is viewed as a promising behavioral endophenotype for bipolar disorder.

While the intra-subject variability in reaction time (ISVRT) is viewed as a promising behavioral endophenotype for bipolar disorder (BD), no studies to date have examined the neural correlates of ISVRT in BD, but the studies in healthy individuals have served as the ground work for such a study to occur. Also, very few functional magnetic resonance imaging (fMRI) studies have been performed to examine the neural endophenotype in individuals with BD, and in those at high risk or at low risk for BD.

ISVRT is a heritable index of sustained attention deficits that can exist in both manic and euthymic adults with BD. In their study, Pagliaccio and colleagues sought to examine the neuroimaging studies of individuals that are diagnosed with BD in order to determine variations in attention across three different groups. Even though attention deficits are a BD endophenotype, no studies to date have made this comparison across low-risk, at-risk, and individuals who were diagnosed with BD. 

The researchers examined 106 participants, aged 8 to 25 years, who had completed a fMRI attention focused task. The participants were a mixture of individuals with BD (n=24), those at risk based on a first degree relative with BD (n=29), and those individuals who were considered healthy and low risk (n=53). The difference among these individuals on ISVRT in reaction time was explored, as well as the connection between reaction time and brain activity, which had not been previously examined in those with BD or those considered to be at risk for BD.

Findings indicate that individuals with BD or those at risk for BD showed increased reaction time variability and the presence of a diminished relationship between reaction time and brain activity in several areas. The blunting across brain regions of the frontal, cingulate, and striatal area was identified in participants who were at risk and in euthymic individuals with BD. The results suggest that the presence of increased ISVRT and blunted RT-blood-oxygen-level dependent signal (BOLD) may be useful endophenotypes for BD. Additionally, the replication of this study’s results across other behavioral paradigms may assist in the early identification, prediction, diagnosis and potential prevention in of those that are considered to be at risk.

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Pagliaccio D, Wiggins JL, Adleman NE, et al. Behavioral and neural sustained attention deficits in bipolar disorder and familial risk for bipolar disorder. Biol Psychiatry. 2016. doi: 10.1016/j.biopsych.2016.09.006. [Epub ahead of print]